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The beneficial effects of genetically engineered Escherichia coli Nissle 1917 in obese C57BL/6J mice

Abstract

Background

Genetically modified probiotics have potential for use as a novel approach to express bioactive molecules for the treatment of obesity. The objective of the present study was to investigate the beneficial effect of genetically modified Escherichia coli Nissle 1917 (EcN-GM) in obese C57BL/6J mice.

Methods

First, an obesity model in C57BL/6J mice was successfully established. Then, the obese mice were randomly assigned into three groups: obese mice (OB), obese mice + EcN-GM (OB + EcN-GM), and obese mice + orlistat (OB + orlistat) (n = 10 in each group). The three groups were gavaged with 0.3 ml of 1010 CFU/ml control EcN, EcN-GM (genetically engineered EcN) and 10 ml/kg orlistat. Body weight, food consumption, fat pad and organ weight, hepatic biochemistry and hepatic histopathological alterations were measured. The effects of EcN-GM on the levels of endocrine peptides and the intestinal microbiota were also analyzed.

Results

After supplementation for 8 weeks, EcN-GM was associated with decreases in body weight gain, food intake, fat pad and liver weight, and alleviation hepatocyte steatosis in obese mice. EcN-GM also increased the level of GLP-1 in serum and alleviated leptin and insulin resistance. Moreover, supplementation with EcN-GM increased the α-diversity of the intestinal microbiota but did not significantly influence the relative abundance of Firmicutes and Bacteroidetes.

Conclusions

These results indicated that EcN-GM, a genetically modified E. coli strain, may be a potential therapeutic approach to treat obesity. The beneficial effect of EcN-GM may be independent of the alteration of the diversity and composition of the intestinal microbiota in obese mice.

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Fig. 1: Effect of EcN-GM on body weight and food intake in obese C57BL/6J mice.
Fig. 2: Effect of EcN-GM on fat pad weight of obese C57BL/6J mice.
Fig. 3: Effect of EcN-GM on organ weight of obese C57BL/6J mice.
Fig. 4: Effect of EcN-GM on the levels of hepatic triglycerides and total cholester in obese C57BL/6J mice.
Fig. 5: Effect of EcN-GM on the levels of GLP-1, leptin and insulin in the serum of obese C57BL/6J mice.
Fig. 6
Fig. 7: Effect of EcN-GM on intestinal microbiota composition.

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Contributions

All authors contributed to this work. JM, JW, and JG designed the experiment. JM and JW performed the experiment. LX and YL analyzed the data. JM and JW drafted the manuscript. JM, LX, and YL prepared the figures. JM, JW, LX, and JG critically revised the manuscript. All the listed authors reviewed and approved the submitted manuscript.

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Correspondence to Jie Ma or Jianwen Gu.

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Ma, J., Wang, J., Xu, L. et al. The beneficial effects of genetically engineered Escherichia coli Nissle 1917 in obese C57BL/6J mice. Int J Obes 46, 1002–1008 (2022). https://doi.org/10.1038/s41366-022-01073-8

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